Kashish Singh / Georg Bunzel / Benjamin Graf / Ka Man Yip / Meina Neumann-Schaal / Holger Stark / Ashwin Chari /
PubMed 要旨
Fatty acids (FAs) play a central metabolic role in living cells as constituents of membranes, cellular energy reserves, and second messenger precursors. A 2.6 MDa FA synthase (FAS), where the ...Fatty acids (FAs) play a central metabolic role in living cells as constituents of membranes, cellular energy reserves, and second messenger precursors. A 2.6 MDa FA synthase (FAS), where the enzymatic reactions and structures are known, is responsible for FA biosynthesis in yeast. Essential in the yeast FAS catalytic cycle is the acyl carrier protein (ACP) that actively shuttles substrates, biosynthetic intermediates, and products from one active site to another. We resolve the S. cerevisiae FAS structure at 1.9 Å, elucidating cofactors and water networks involved in their recognition. Structural snapshots of ACP domains bound to various enzymatic domains allow the reconstruction of a full yeast FA biosynthesis cycle. The structural information suggests that each FAS functional unit could accommodate exogenous proteins to incorporate various enzymatic activities, and we show proof-of-concept experiments where ectopic proteins are used to modulate FAS product profiles.
EMDB-17839, PDB-8prv: Asymmetric unit of the yeast fatty acid synthase in the non-rotated state with ACP at the ketosreductase domain (FASamn sample) 手法: EM (単粒子) / 解像度: 2.9 Å
EMDB-17842, PDB-8ps1: Asymmetric unit of the yeast fatty acid synthase in the non-rotated state with ACP at the ketosynthase domain (FASamn sample) 手法: EM (単粒子) / 解像度: 2.8 Å
EMDB-17846, PDB-8ps8: Asymmetric unit of the yeast fatty acid synthase in the semi non-rotated state with ACP at the enoyl reductase domain (FASam sample) 手法: EM (単粒子) / 解像度: 4.0 Å
EMDB-17847, PDB-8ps9: Asymmetric unit of the yeast fatty acid synthase in the non-rotated state with ACP at the ketosynthase domain (FASam sample) 手法: EM (単粒子) / 解像度: 2.9 Å
EMDB-17848, PDB-8psa: Asymmetric unit of the yeast fatty acid synthase in the semi non-rotated state with ACP at the ketosynthase domain (FASam sample) 手法: EM (単粒子) / 解像度: 3.6 Å
EMDB-17851, PDB-8psf: Asymmetric unit of the yeast fatty acid synthase in non-rotated state with ACP at the acetyl transferase domain (FASx sample) 手法: EM (単粒子) / 解像度: 2.8 Å
EMDB-17852, PDB-8psg: Asymmetric unit of the yeast fatty acid synthase in the semi non-rotated state with ACP at the acetyl transferase domain (FASx sample) 手法: EM (単粒子) / 解像度: 3.7 Å
EMDB-17853, PDB-8psj: Asymmetric unit of the yeast fatty acid synthase in the semi rotated state with ACP at the acetyl transferase domain (FASx sample) 手法: EM (単粒子) / 解像度: 3.4 Å
EMDB-17854, PDB-8psk: Asymmetric unit of the yeast fatty acid synthase in the non-rotated state with ACP at the ketosynthase domain (FASx sample) 手法: EM (単粒子) / 解像度: 2.8 Å
EMDB-17855, PDB-8psl: Asymmetric unit of the yeast fatty acid synthase in the semi non-rotated state with ACP at the ketosynthase domain (FASx sample) 手法: EM (単粒子) / 解像度: 3.7 Å
EMDB-17856, PDB-8psm: Asymmetric unit of the yeast fatty acid synthase in the non-rotated state with ACP at the malonyl/palmitoyl transferase domain (FASx sample) 手法: EM (単粒子) / 解像度: 3.1 Å
EMDB-17859, PDB-8psp: Asymmetric unit of the yeast fatty acid synthase in rotated state with ACP at the acetyl transferase domain (FASx sample) 手法: EM (単粒子) / 解像度: 2.9 Å